TY-2719 / TYK Medicines - LARVOL DELTA

The EGFR-PROTAC molecule TY-2719 attenuates acquired resistance to 3rd-generation EGFR TKIs and augments the efficacy of KRAS mutant inhibitors in solid tumors (AACR 2026) - "TY-2719 overcame osimertinib resistance in BaF3 L858R/C797S and BaF3 del19/C797S CDX mouse models and enhanced the efficacy of Divarasib (GDC-6036) and pan-KRASi Daroxonrasib (RMC-6236) in NSCLC H1972 and H2122 cells, as well as Daroxonrasib in MiaPaca 2 (PDAC, KRAS G12D), AsPC-1, SU.86.86, PANC-1 (PDAC, KRAS G12D), and Capan-1 (PDAC KRAS G12V). TY-2719 effectively degraded EGFR with the L858R mutation in NSCLC H3255 cells and the L858R/T790M/C797S and 19del/C797S mutations in BaF3 cells. However, it did not degrade EGFR in cells expressing wild-type EGFR, such as A549 and H358 cells. It demonstrated excellent antiproliferative activity against EGFR mutants but did not inhibit the growth of normal cells, including NHEK, MCF-10A, IOSE-80, and FHC cells."

Clinical • Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Ductal Adenocarcinoma • Solid Tumor • KRAS

TY-2719, a potent and selective broad-spectrum mutation-effective EGFR-PROTAC molecule, attenuates acquired resistance to 3rd-generation EGFR TKIs (AACR 2025) - P1 | "These included CFT8919 (NCT06641609), HSK40118 (NCT06050980), and HJ-002-03 (CTR20241691). TY-2719 did not suppress the growth of normal cells, such as NHEK, and NSCLC cells, such as A549 and A431 cells harboring wild-type EGFR. However, TY-2719 has excellent in vitro antiproliferative activity against a number of EGFR mutants, including common mutations, post osimertinib-resistant mutations, and rare mutations. Our data suggest that TY-2719 has superior selective activity in cells containing EGFR mutants compared to wild-type EGFR-expressing cells."

Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CRBN • GSPT1 • IKZF1

TYK Medicines…is pleased to announce that the research progress and results for five innovative drug projects under development of the Company, namely TY-0609 (CDK4 inhibitor), TY-2699a (CDK7 inhibitor), TY-2719 (EGFR/FAK (PROTAC) inhibitor), PI3Kα (PI3Kα inhibitor), and TY-1054 (YAP-TEAD inhibitor), will be presented by the Company in poster presentation at 2026…AACR annual meeting (HKEXnews)

Preclinical • Solid Tumor